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Alzheimer’s disease: pathogenesis, diagnostics, and therapeutics

Authors Tiwari S, Atluri V, Kaushik A, Yndart A, Nair M

Received 5 January 2019

Accepted for publication 2 March 2019

Published 19 July 2019 Volume 2019:14 Pages 5541—5554

DOI https://doi.org/10.2147/IJN.S200490

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 2

Editor who approved publication: Dr Thomas J Webster


Sneham Tiwari, Venkata Atluri, Ajeet Kaushik, Adriana Yndart, Madhavan Nair

Department of Immunology and Nano-Medicine, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA

Abstract: Currently, 47 million people live with dementia globally, and it is estimated to increase more than threefold (∼131 million) by 2050. Alzheimer’s disease (AD) is one of the major causative factors to induce progressive dementia. AD is a neurodegenerative disease, and its pathogenesis has been attributed to extracellular aggregates of amyloid β (Aβ) plaques and intracellular neurofibrillary tangles made of hyperphosphorylated τ-protein in cortical and limbic areas of the human brain. It is characterized by memory loss and progressive neurocognitive dysfunction. The anomalous processing of APP by β-secretases and γ-secretases leads to production of Aβ40 and Aβ42 monomers, which further oligomerize and aggregate into senile plaques. The disease also intensifies through infectious agents like HIV. Additionally, during disease pathogenesis, the presence of high concentrations of Aβ peptides in central nervous system initiates microglial infiltration. Upon coming into vicinity of Aβ, microglia get activated, endocytose Aβ, and contribute toward their clearance via TREM2 surface receptors, simultaneously triggering innate immunoresponse against the aggregation. In addition to a detailed report on causative factors leading to AD, the present review also discusses the current state of the art in AD therapeutics and diagnostics, including labeling and imaging techniques employed as contrast agents for better visualization and sensing of the plaques. The review also points to an urgent need for nanotechnology as an efficient therapeutic strategy to increase the bioavailability of drugs in the central nervous system.

Keywords: amyloid beta, amyloidogenesis, amyloid precursor proteins, β-secretases, γ-secretases, tau phosphorylation


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